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M N Marsh

Publications and source records attributed to M N Marsh.

81 records · Page 5Linked to original sources

Observations of isolated enterocytes and of their subcellular components using transmission and scanning electron microscopy.

Isolated epithelial cells and their subcellular organelles were examined both by transmission and by scanning electron microscopy. It was shown that scanning electron microscopy is particularly useful for displaying the three-dimensional structure of the brush border. Furthermore, it has been possible to observe the basal aspect of separated epithelium for the first time. Studies on the scanning electron microscopic appearance of isolated nuclei, mitochondria, and lysosomes did not reveal any evidence of surface structure.

Animals↗

The interactive role of mucosal T lymphocytes in intestinal growth, development and enteropathy.

Over the past 15-20 years, research has progressively focused on the mucosal T cell as the central factor in the initiation of physiological or pathological changes, first in the growth and maturation of the early (postnatal) intestine, and second in adult-type enteropathies resulting from sensitivity to either food or pathogen-derived antigens. T cell-mediated events may be measured, for example, in terms of specific immunopathologic patterns of change and injury, such as type 1 (lymphocyte infiltration), type 2 (crypt hyperplasia) and type 3 (flat-destructive), which can be recognized and quantitated microscopically; by determination of lymphocyte reactivity through secretion of interleukin-2 receptors (IL-2R) into plasma or expression by mucosal lymphocytes; by quantitation of lymphocyte subsets emigrating into inflamed tissues by immunoperoxidase-labelled monoclonal antibodies; or by the determination of T cell receptor polymorphisms. Alterations in intestinal growth, structure and function at weaning are likely to be T cell-mediated as they are analogous to the same type 1/2 lesions that reflect modulation of adult mucosal architecture in food and parasite-induced hypersensitivity reactions. Enteropathies associated with HIV infection and T cell deficiency display a milder degree of villous flattening and impaired crypt hyperplasia than that typical of gluten-sensitivity, suggesting a reversion to lesser degrees of mucosal pathology (type 1/2). Clearly more information will accrue; meanwhile the remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function.

Animals↗

The immunopathology of the small intestinal reaction in gluten-sensitivity.

Computerised image-analysis was used to define the spectrum of immunopathological changes in small intestinal mucosa in established celiac sprue disease; dermatitis herpetiformis; 1 degree relatives of celiac sprue patients, and treated celiac sprue patients challenged with varying doses of a peptic-tryptic digest of gluten. Typically, in flat ('Type 2') lesion there was a reduced number of large, mitotically active lymphocytes in surface epithelium, but an increased lymphocyte population in crypts. In approximately 50% untreated DH patients and in 20% 1 degree celiac sprue relatives, mucosal architecture was well-preserved although surface (villous) epithelium contained an expanded population of small, non-mitotic lymphocytes ('Type 1' lesion), with or without crypt hyperplasia. Similar changes were also induced by small dose gluten challenge. Larger dose challenges caused a progression from a Type 1 to a Type 2 lesion during a 5 day period of observation. In addition, observations on a few patients over 2-4 years showed a similar sequence of mucosal changes. A major feature of this sequence was the early appearance of crypt hypertrophy, before significant villous flattening had occurred. These changes parallel T lymphocyte-mediated graft- versus-host reactions in animals, suggesting that the specific immunopathologic features seen in gluten sensitivity are fundamentally cell-mediated in type, the degree of change probably dependent on host genetic factors. Finally, these data show that in becoming flat the mucosa must initially pass through the earlier Type 1 lesion in which crypt hypertrophy is a prominent response.

Adult↗